PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease.
PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease.
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PNPLA3 rs738409 是非酒精性脂肪肝治疗反应的基础。
DOI：
10.12998/wjcc.v6.i8.167
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发表时间：
2018-08-16
影响因子：
1.1
通讯作者：
Pan Q
中科院分区：
文献类型：
--
作者：
Wang JZ;Cao HX;Chen JN;Pan Q
非酒精性脂肪性肝病（NAFLD）目前已成为慢性肝病的主要原因，其发病率在全球范围内不断上升。Patatin-like phospholipase domain-containing protein 3（PNPLA 3）rs738409 C > G反映了赋予NAFLD高风险的关键遗传因素之一。然而，PNPLA 3多态性在NAFLD治疗中的作用仍然不确定。在这里，本综述揭示了G等位基因在PNPLA 3 rs738409（PNPLA 3 148 M变异）的NAFLD患者对生活方式改变，二肽基肽酶-4抑制剂和减肥手术的治疗敏感。与C等位基因携带者相比，他们表现出肝脏脂肪含量显著降低，体重减轻，胰岛素抵抗消除。相比之下，携带PNPLA 3 rs738409 C-等位基因（PNPLA 3 148 I变体）而不是G-等位基因的患者通过ω-3多不饱和脂肪酸和他汀类药物干预表现出更大的有益效果。改善的脂肪组织-肝脏相互作用和肝内甘油三酯流出的减少可能有助于PNPLA 3 rs738409相关的治疗功效的改善。因此，PNPLA 3 rs738409是对各种治疗的反应的基础，这保证了基于基因型分层的NAFLD的个性化，精确的药物。
Non-alcoholic fatty liver disease (NAFLD) has now become the leading cause of chronic liver disease with its growing incidence worldwide. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C > G reflects one of the critical genetic factors that confers high-risk to NAFLD. However, the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain. Here, the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409 (PNPLA3 148M variant) are sensitive to therapies of lifestyle modification, dipeptidyl peptidase-4 inhibitors, and bariatric surgery. They exhibit much significant reduction of liver fat content, in concurrence with weigh loss and abolished insulin resistance, as compared to those of C-allele carriers. In contrast, patients bearing PNPLA3 rs738409 C-allele (PNPLA3 148I variant), instead of G-allele, demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention. Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409 related diversities in therapeutic efficacy. Therefore, PNPLA3 rs738409 underlies the response to a variety of treatments, which warrants a personalized, precise medicine in NAFLD on the basis of genotype stratification.
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影响因子：
4.2
作者：
Kan, Hiromi;Hyogo, Hideyuki;Chayama, Kazuaki
通讯作者：
Chayama, Kazuaki
影响因子：
9.3
作者：
Jiménez-Agüero R;Emparanza JI;Beguiristain A;Bujanda L;Alustiza JM;García E;Hijona E;Gallego L;Sánchez-González J;Perugorria MJ;Asensio JI;Larburu S;Garmendia M;Larzabal M;Portillo MP;Aguirre L;Banales JM
通讯作者：
Banales JM
影响因子：
--
作者：
Fukuhara, Takayuki;Hyogo, Hideyuki;Chayama, Kazuaki
通讯作者：
Chayama, Kazuaki
影响因子：
29.4
作者：
Chalasani, Naga;Younossi, Zobair;Sanyal, Arun J.
通讯作者：
Sanyal, Arun J.
影响因子：
39.2
作者：
Bellentani, S;Saccoccio, G;Tiribelli, C
通讯作者：
Tiribelli, C